ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.5225A>G (p.Asn1742Ser)

gnomAD frequency: 0.00002  dbSNP: rs745407845
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000206576 SCV000259698 uncertain significance Neurofibromatosis, type 1 2023-12-21 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1721 of the NF1 protein (p.Asn1721Ser). This variant is present in population databases (rs745407845, gnomAD 0.01%). This missense change has been observed in individual(s) with neurofibromatosis type 1 and breast cancer (PMID: 26740943, 31882575). This variant is also known as c.5225A>G, p.Asn1742Ser. ClinVar contains an entry for this variant (Variation ID: 219686). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NF1 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002317731 SCV000670373 likely benign Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2021-04-02 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV001545516 SCV001764862 uncertain significance not provided 2019-06-21 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 29684080, 26740943)
Genome-Nilou Lab RCV000206576 SCV002560524 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002494519 SCV002786214 uncertain significance Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2021-09-28 criteria provided, single submitter clinical testing
Laboratory of Medical Genetics Unit, Bambino Gesù Children's Hospital RCV003313057 SCV004012936 uncertain significance Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype 2018-10-09 criteria provided, single submitter research

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